Determinants of positive cervical cancer screening among reproductive‐age women in South Wollo Zone, Northeast Ethiopia

Abstract Background Cervical cancer is one of the reproductive organ cancers found in women which commonly arises from the cervix. It is the second most prevalent cancer among women in developing countries including Ethiopia. However, the association between positive cervical cancer screening and modifiable behavioral risk has not been well characterized in developing countries. Objective To identify determinants of positive cervical cancer screening among reproductive‐age women in the South Wollo Zone, Amhara region, northeast Ethiopia. Method An unmatched case‐control study design was conducted from January 28 to April 12, 2020 in the South Wollo Zone. Four hundred ten clients participated in the study with 82 cases 328 controls. Study subjects were selected by systematic random sampling. Data entered using Epi data version 3.1 and analyzed using SPSS version 24. A bivariable and multivariable logistic regression model was done. The adjusted odds ratio with its 95% confidence interval (CI) was used to measure the strength and direction of the association and P‐value <.05 was declared as significant. Results A total of 410 study subjects have participated with a 100% response rate. The mean age of respondents was found to be 35.58 (±8.05) years. Study participants having a history of sexually transmitted infections (adjusted odds ratio [AOR] = 3.69, 95% CI [1.70‐8.01]), having poor knowledge about cervical cancer (AOR = 2.31, 95% CI [1.32‐4.02]) and two or more lifetime sexual partners of women and husbands (AOR = 2.80, 2.55, 95% CI [1.22‐6.44, 1.28‐5.06]) respectively were independent predictors of positive cervical cancer screening. Conclusion and recommendation Risk factors that determine positive cervical cancer screening were identified. Comprehensive strategies that are focused on addressing sexual behavior and knowledge gaps should be designed. Efforts on improving and cultivating those significant factors should be done by stakeholders to prevent cervical cancer.

improving and cultivating those significant factors should be done by stakeholders to prevent cervical cancer.

K E Y W O R D S
case-control, Ethiopia, positive cervical cancer screening, South Wollo Zone

| INTRODUCTION
Cervical cancer is one of the reproductive organ cancers found in women which commonly arises from the cervix. 1 It is mainly caused by Human Papilloma Virus (HPV). [2][3][4] Cervical cancer is preventable in most cases and curable if identified and treated in its precancerous stage. 5 Cervical cancer is the second most prevalent cancer among women in developing countries including Ethiopia, and the largest killer cancer among women in those countries. 6 Worldwide, a population of 2784 million women aged 15 years and older are at risk of developing cervical cancer. 7 In Africa, according to the most recent estimates, 80 400 women are diagnosed with cervical cancer every year, the second most frequent cancer. 50 300 die from the disease every year. Rates vary substantially across regions, with the incidence and death rates in East Africa, 7,8 the region of Ethiopia belongs to, and West Africa five times as high as the rates in North Africa. 8 In Ethiopia 29.43 million women ages 15 years and older are at risk of developing cervical cancer. 10 Current estimates showed that 7095 women were newly diagnosed with cervical cancer and 4732 deaths resulting from it occur every year. 9 Cervical cancer ranks as the second most frequent cancer among women in Ethiopia and between 15 and 44 years of age with an age-standardized incidence rate of 26.4 per hundred thousand. 7,9 Cervical cancer causes the highest mortality rate compared to other types of cancers among women in Ethiopia. 10 Cervical cancer has exerted negative consequences on health, economic, and social conditions. The national guideline for cervical cancer prevention and control in Ethiopia showed that the majority of cancers (over 80%) in developing countries especially sub-Saharan Africa are detected at a late stage. 11 Nowadays HPV vaccine started in Ethiopia among 9 to 14 years school children starting from 2018, unfortunately still morbidity and mortality due to cervical cancer are high. This is attributable to low knowledge and generally poor health-seeking behavior. 11,12 Evidence indicates that a significant part of the burden of cervical cancer is potentially prevented by early screening and treatment or by reducing and eliminating the risk factors. 13,14 Therefore, the "Ethiopian health sector transformation plan includes the national strategies of cervical cancer prevention and control programs to improve the health status of women." 5 However, the association between positive cervical cancer screening and modifiable behavioral risk has not been well characterized in the South Wollo Zone, Northeast Ethiopia. Therefore, this study was conducted to explore determinants of positive pre-cervical lesion among women found in the South Wollo Zone.
The finding of this study will help to plan appropriate intervention at all levels in the study area to improve the gap in cervical cancer prevention and control programs. Moreover, it will be used by other researchers as a baseline in future study.

| Study design, area and period
A facility-based unmatched case-control study was conducted in the South Wollo Zone from January 28, 2020 to April 12, 2020. The zone has a total of 10 primary hospitals, 129 health centers, 523 health posts, 134 private primary clinics, 47 medium clinics, and 1 nongovernmental health facility which gives preventive and curative services to the people. Twenty-one health facilities provide cervical cancer screening and treatment services, which are 7 primary hospitals, one Family Guidance Association Ethiopia (FGAE) clinic, and 13 health centers.

| Population and eligibility criteria
The source populations of cases were all women aged from 21 to 65 years with positive Pap smear results in the South Wollo Zone.
The source populations for controls were all women aged from 21 to 65 years, who had Pap smear-negative results. Women who had VIA positive test results for cases and VIA negative test results for controls in the randomly selected cervical cancer screening and treatment health facilities were study populations of this study. Severely ill clients not able to give responses were excluded from the study.

| Sample size determination and procedure
The sample size was determined using Epi-info version 7.1 by considering the assumptions proportion of women with a negative result from VIA who were exposed to multiple sexual partners as 30.57%, 95% CI, 80% power of the test with an adjusted odds ratio (AOR) of 2.17 and a 1:4 ratio of cases to controls shown in other studies. 15 A total sample size of 410 was determined, including 82 cases and 328 controls, which also accounted for 10% non-response. Among 21 health facilities, 6 health facilities were randomly selected using the lottery method and the total sample size was allocated to each selected health facility using proportional allocation according to average monthly client flow. The study subjects were selected using systematic random sampling from health facility flow.

| Data collection procedures
Data were collected using pretested structured questionnaire through face-to-face interviews administered; in-person by 10 trained BSC midwifery or nurses at the health facility level and the daily collected data were checked by trained supervisors. Questionnaires included socio-demographic characteristics, reproductive health characteristics, lifestyle, sexual behavior characteristics, and knowledge of study subjects about cervical cancer. 15,16,18,20 2.5 | Data quality assurance The questionnaire was prepared in English and translated into Amharic. It was checked for consistency by back-translation to English. A pre-test was done and the data collection process was strictly supervised and data were checked for consistency and completeness daily. Incomplete and unclear questionnaires were returned to interviewers to be completed. The internal consistency of the knowledge questionnaire was checked using Cronbach's alpha value which was 0.88. Finally, the entered data were checked for completeness at the beginning, middle, and the last stage of the work and data cleaning was done at the end of the data entry.

| Data processing and analysis
Data were entered into Epi data version 3.1 and then exported to SPSS version 24 for analysis. Data cleaning was done by running frequencies, cross-tabulation, and sorting among reported cases or variables. The knowledge status of respondents about cervical cancer was identified by doing a composite analysis. A binary logistic regression analysis was done to describe the association between independent and dependent variables and a multivariable logistic regression analysis was used to show factors determining outcome variables. Variables that had a P-value of .25 or less in the binary logistic regression were included in the multivariable logistic regression. Finally, the adjusted odds ratio with its 95% confidence interval (CI) with P-value <.05 was considered statistically significant for all independent variables at the multivariable logistic regression. Before the final model Multicollinearity test was checked using variance inflation factors (VIF), to see the correlation between independent variables but, no collinearity was detected. The goodness of the model was checked by Hosmer-Lemeshow's test statistic which was not significant.

| Operational definitions
Case: A case was a woman aged from 21 to 65 years with positive for Visual Inspection of Acetic Acid (VIA) finding within 3 months before and during the actual data collection period. 31 Control: A control was a woman aged 21 to 65 years with negative VIA finding during the actual data collection period. 31 Knowledge: Out of 12 knowledge-related questions, the respondents who respond sample mean score and above were classified as having "good Knowledge," while those who responded below the sample mean score (0.01) were classified as having "poor Knowledge." 29 Multiple sexual partners: Women who have experienced two or more sexual partners in their lifetime.
Contraceptive history: Women who had the experience of any type of contraceptive use.
The user of contraceptive pills: Women who use oral contraceptive pills for family planning.

| Socio-demographic characteristics
All case and control women expected were interviewed which yields a 100% response rate. The mean age of cases and controls was found to be 35

| Reproductive health-related characteristics
Of all respondents, 62 (75%) of cases and 233 (71%) of controls had been ever used contraceptives. Regarding the duration of contraceptive

| Lifestyle and sexual behavior related characteristics
Among respondents, 17 (20.7%) of cases and 41 (12.5%) of controls were previously screened for cervical cancer in their lifetime (Table 3). knowledge about cervical cancer were identified as predictors of positive cervical cancer screening.
Women who had a history of sexually transmitted infections were 3.69 times more likely to be positive cervical cancer screening as compared to those women who did not have a history of sexually transmitted infections. This finding is similar to a study done in Addis Abeba, Adama town in Ethiopia and Nairobi Kenya, Zimbabwe. 23,30 But it is different from the study done in Yergalem General hospital southern Ethiopia those where women who had a history of STI were less likely to have positive cervical cancer screening than this study finding. 31 This might be due to sampling size, study design, sociocultural and population characteristics differences. The implication of this finding might be due to a lack of comprehensive and complemented service provision on STI and cervical cancer prevention and control.
Women who had two or more lifetime sexual partners were 2.80 times more likely to have positive cervical cancer screening than those who did not have two or more lifetime sexual partners. This showed that an increase in the number of sexual partners has raised the risk of developing cervical cancer. This finding is consistent with the study conducted in Addis Abeba, Adama town and Tigray region, Ethiopia. 23 But it is different from the study done in Yergalem General Hospital in Ethiopia those where women who had two or more lifetime sexual partners were less likely to have positive cervical cancer screening than this study finding. 31 This might be due to study design, sociocultural and sample size differences. Moreover, having multiple sexual partners increases the risk of infection with high-risk human papillomavirus (HPV). 32 In this study, women who had a history of lifetime multiple sexual partners were positively associated with positive cervical cancer screening. However, in the study conducted in North Central Nigeria, those who had two or more lifetime sexual partners were negatively associated with the risk of developing cervical cancer. 31 This might be due to socio-demographic, cultural, and study design differences. The implication of this finding might be due to improper implementation of behavioral change communication strategies to change or limit lifetime multiple sexual practices among women. And also, women might not understand the impact of multiple sexual partners as a risk factor of cervical cancer.
Women whose husbands had two or more lifetime sexual partners were 2.55 times more likely to develop Positive cervical cancer screening than those women whose husbands had no two or more lifetime sexual partners. This finding is consistent with the study done in Algeria, Addis Abeba and Jimma university specialized hospital southwest Ethiopia,. 23 Furthermore, early sexual activity and multiple sexual partners are cofactors that are independently associated with abnormal cytology and cervical cancer. 34 This is higher because those women have a higher risk of acquiring HPV infection, which is the causative agent for cervical cancer. 35 The implication of this finding might be due to improper implementation of behavioral change communication strategies to change or limit lifetime multiple sexual practices among husbands. And also, husbands might not understand the impact of multiple sexual partners as a risk factor of cervical cancer.
This needs strong intervention to improve risky sexual behaviors among youths School-based education can be a solution for boys and girls at younger ages at youth centers to reach out to school youths. Zonal health department and health facilities including health professionals for their unlimited co-operation in facilitating the study.

FUNDING
The research got a grant from Amhara Region Health Bureau However; the granting agency has no role in the design of the study and collection, analysis, and interpretation of data, and in writing the manuscript.

CONFLICT OF INTEREST
The authors declare that they have no competing interests. AM-initiation of the study, design, analysis, and writing of the manuscript, NC and EA-assisted in the design, participated in organizing the data collection process, analysis, and report writing, and writing the manuscript. All authors read and approved the final manuscript and have an equal contribution.

TRANSPARENCY STATEMENT
The lead author (Niguss Cherie) affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

DATA AVAILABILITY STATEMENT
The data supporting the findings of this study are available from the corresponding author upon request. The corresponding author had full access to all of the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis.

ETHICS STATEMENT
The study protocol was approved by the Institutional Research